VEGF gene transfer to prevent coronary artery restenosis

该提案旨在研究编码VEGF-1 （VEGF A）基因165个氨基酸异构体的裸DNA作为PTCA辅助物的动脉基因转移。《建议》有以下三个具体目标。特定目的#1：确定冠状动脉基因转移的安全性，以加速经皮腔内冠状动脉成形术（PTCA）后的再内皮化（rET）。具体目标2：获得关于冠状动脉基因转移预防再狭窄的生物活性的初步数据。具体目的#3：确定phVEGF165冠状动脉基因转移对PTCA靶部位以外冠状动脉粥样硬化进展的影响。在基因转移后，将对参加本研究的患者进行各种评估。将进行一系列临床检查，包括标准病史和体格检查，以及标准实验室检查，以证明phVEGF165冠状动脉基因转移的安全性。患者的状态将通过非侵入性测试（运动前和运动后测试-包括核灌注扫描）和侵入性测试（定量冠状动脉病变和血管内超声）进一步监测。后一项审查对于实现具体目标2和3尤为重要。我们期望这项研究的结果能够建立安全性，并潜在地提供有关疗效的见解，这将有助于指导在II期试验中进一步测试这一拟议治疗策略的价值。

This Proposal has been designed to investigate arterial gene transfer of naked DNA encoding for the 165-amino acid isoform of the VEGF-1 (VEGF A) gene as an adjunct to PTCA. The Proposal has the following three Specific Aims. Specific Aim #1: to determine the safety of coronary gene transfer of phVEGF165 to accelerate re-endothelialization (rET) following percutaneous transluminal coronary angioplasty (PTCA) in patients (pts) with stenotic or occluded native coronary arteries. Specific Aim #2: to obtain preliminary data regarding bioactivity of coronary gene transfer of phVEGF165 for prevention of restonosis. Specific Aim #3: to determine the impact of phVEGF165 coronary gene transfer on the progression of atherosclerosis involving coronary arterial sites other than PTCA target sites. A variety of assessments will be performed among the patients enrolled in this study following gene transfer. Serial clinical examinations- including standard history and physical examinations-along with standard laboratory tests will be performed to document the safety of phVEGF165 coronary gene transfer. The patients' status will be further monitored by both non-invasive tests (pre- and post-exercise testing-including nuclear perfusion scans) and invasive testing )pre- and post-quantitative coronary angiopathy and intravascular ultrasound). These latter examinations will be particularly critical for addressing Specific Aims 2 and 3. It is our anticipation that the findings of this study should establish the safety- and potentially provide insights regarding efficacy- that would help to guide decisions regarding the value of testing this proposed therapeutic strategy further in Phase II trials.